In medical diagnosis, relying on only one type of biomarker is insufficient to accurately identify cancer. Blood-based multicancer early detection can help identify more than one type of cancer from a single blood sample. In this study, a super-resolution multispectral imaging nanoimmunosensor (srMINI) based on three quantum dots (QDs) of different color conjugated with streptavidin was developed for the simultaneous screening of various cancer biomarkers in blood at the single-molecule level. In the experiment, the srMINI chip was used to simultaneously detect three key cancer biomarkers: carcinoembryonic antigen (CEA), C-reactive protein (CRP), and alpha-fetoprotein (AFP). The srMINI chip exhibited 108 times higher detection sensitivity of 0.18-0.5 ag/mL (1.1-2.6 zM) for these cancer biomarkers than commercial enzyme-linked immunosorbent assay kits because of the absence of interfering signals from the substrate, establishing considerable potential for multiplex detection of cancer biomarkers in blood. Therefore, the simultaneous detection of various cancer biomarkers using the developed srMINI chip with high diagnostic precision and accuracy is expected to play a decisive role in early diagnosis or community screening as a single-molecule biosensor.

Emerging blood-based multicancer early-detection (MCED) tests may redefine cancer screening, reduce mortality, and address health disparities if their benefit is demonstrated. U.S. payers\' coverage policies will impact MCED test adoption and access; thus, their perspectives must be understood. We examined views, coverage barriers, and evidentiary needs for MCED from 19 private payers collectively covering 150 000 000 enrollees. Most saw an MCED test\'s potential merit for cancers without current screening (84%), but fewer saw its merit for cancers with existing screening (37%). The largest coverage barriers were inclusion of cancers without demonstrated benefits of early diagnosis (73%), a high false-negative rate (53%), and lack of care protocols for MCED-detected but unconfirmed cancers (53%). The majority (58%) would not require mortality evidence and would accept surrogate endpoints. Most payers (64%) would accept rigorous real-world evidence in the absence of a large randomized controlled trial. The majority (74%) did not expect MCED to reduce disparities due to potential harm from overtreatment resulting from an MCED and barriers to downstream care. Payers\' perspectives and evidentiary needs may inform MCED test developers, researchers producing evidence, and health systems framing MCED screening programs. Private payers should be stakeholders of a national MCED policy and equity agenda.

BACKGROUND: Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the \"intended effect\" (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests.
METHODS: We simulated hypothetical MCD screening trials to compare power and sample size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial [NLST], Minnesota Colon Cancer Control Study [MINN-FOBT-A], and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial-colorectal component [PLCO-CRC]).
RESULTS: Compared with the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality P values 5-fold (NLST), 33-fold (MINN-FOBT-A), or 14 160-fold (PLCO-CRC) or, alternately, reduced sample size (90% power) by 26% (NLST), 48% (MINN-FOBT-A), or 59% (PLCO-CRC). For potential MCD trial designs requiring 100 000 subjects per arm to achieve 90% power for multicancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37 500-50 000 per arm, depending on assumptions concerning control-arm test-positives.
CONCLUSIONS: Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample size or accelerate trials and could provide particularly strong power gains for MCD tests.

BACKGROUND: Guidelines-driven screening protocols for early cancer detection in dogs are lacking, and cancer often is detected at advanced stages.
OBJECTIVE: To examine how cancer typically is detected in dogs and whether the addition of a next-generation sequencing-based \"liquid biopsy\" test to a wellness visit has the potential to enhance cancer detection.
METHODS: Client-owned dogs with definitive cancer diagnoses enrolled in a clinical validation study for a novel blood-based multicancer early detection test.
METHODS: Retrospective medical record review was performed to establish the history and presenting complaint that ultimately led to a definitive cancer diagnosis. Blood samples were subjected to DNA extraction, library preparation, and next-generation sequencing. Sequencing data were analyzed using an internally developed bioinformatics pipeline to detect genomic alterations associated with the presence of cancer.
RESULTS: In an unselected cohort of 359 cancer-diagnosed dogs, 4% of cases were detected during a wellness visit, 8% were detected incidentally, and 88% were detected after the owner reported clinical signs suggestive of cancer. Liquid biopsy detected disease in 54.7% (95% confidence interval [CI], 49.5%-59.8%) of patients, including 32% of dogs with early-stage cancer, 48% of preclinical dogs, and 84% of dogs with advanced-stage disease.
CONCLUSIONS: Most cases of cancer were diagnosed after the onset of clinical signs; only 4% of dogs had cancer detected using the current standard of care (i.e., wellness visit). Liquid biopsy has the potential to increase detection of cancer when added to a dog\'s wellness visit.

Multicancer Early Detection (MCED) represents a new and exciting paradigm for the early detection of cancer, which is the leading cause of death worldwide. Current screening tests, recommended for only five cancer types (breast, lung, colon, cervical, and prostate), are limited by a lack of complete adherence to guideline-based use and by the fact that they have cumulative high false positive rates. MCED tests agnostically detect cancer signals in the blood with good sensitivity and low false positive rates, can predict the cancer site of origin with high accuracy, can detect highly lethal cancers that have no current screening tests, and promise to improve cancer screening by improving efficiency and reducing the overall number needed to screen. Herein we outline this promise and clarify several published misconceptions about this field.

Imaging plays an integral role in the initial diagnosis and longitudinal care of patients with cancer. Liquid biopsies, which most commonly involve genetic analysis of circulating free DNA, have emerged as important complementary tools in cancer care with the potential to interface with imaging at each step of the cancer care continuum. Here, the authors use non-small-cell lung cancer as a paradigm to elucidate factors driving the need for liquid biopsy in the spectrum of lung cancer care, demonstrate ways in which liquid biopsy has already changed standard clinical practice, and discuss anticipated synergies of liquid biopsy and imaging in screening and early detection and in monitoring of disease.

Multicancer screening is a promising approach to improving the detection of preclinical disease, but current technologies have limited ability to identify precursor or early stage lesions, and approaches for developing the evidentiary chain are unclear. Frameworks to enable development and evaluation from discovery through evidence of clinical effectiveness are discussed.

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